With the aim to investigate the effect of different heterocyclic rings linked to the 4-aminoquinoline nucleus on the antimalarial activity, a set of 7-chloro-N-(heteroaryl)-methyl-4-aminoquinoline and 7-chloro-N-(heteroaryl)-4-aminoquinoline was synthesized and tested in vitro against D-10 (CQ-S) and W-2 (CQ-R) strains of Plasmodium falciparum. All compounds exhibited from moderate to high antiplasmodial activities. The activity was strongly influenced both by the presence of a methylenic group, as a spacer between the 4-aminoquinoline and the heterocyclic ring, and by the presence of a basic head. The most potent molecules inhibited the growth of both CQ-S and CQ-R strains of P. falciparum with IC(50)<30nM and were not toxic against human endothelial cells. These results confirm that the presence of an heteroaryl moiety in the side chain of 7-chloro-4-aminoquinoline is useful for the design and development of new powerful antimalarial agents.
Synthesis and antiplasmodial activity of new heteroaryl derivatives of 7-chloro-4-aminoquinoline / M. Casagrande, A. Barteselli, N. Basilico, S. Parapini, D. Taramelli, A. Sparatore. - In: BIOORGANIC & MEDICINAL CHEMISTRY. - ISSN 0968-0896. - 20:19(2012 Aug 02), pp. 5965-5979.
|Titolo:||Synthesis and antiplasmodial activity of new heteroaryl derivatives of 7-chloro-4-aminoquinoline|
CASAGRANDE, MANOLO (Primo)
BARTESELLI, ANNA (Secondo)
TARAMELLI, DONATELLA (Penultimo)
SPARATORE, ANNA CONCETTINA (Ultimo)
|Parole Chiave:||4-Aminoquinoline derivatives; Antimalarial agents; Chloroquine; Plasmodium falciparum|
|Settore Scientifico Disciplinare:||Settore CHIM/08 - Chimica Farmaceutica|
Settore MED/04 - Patologia Generale
Settore MED/07 - Microbiologia e Microbiologia Clinica
|Data di pubblicazione:||2-ago-2012|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.bmc.2012.07.040|
|Appare nelle tipologie:||01 - Articolo su periodico|